The elucidation of the mechanisms of enzyme-catalyzed reactions remains a vital and fascinating area of both bioorganic and bioinorganic chemistry. As a result of such studies, nature advances our understanding of chemical processes, and chemistry helps us understand biological processes. Work in this lab focuses on the enzymology of RNA modification. 

The ubiquity of chemical alteration of bases in the primary transcripts of RNA attests to the important cellular roles that these modifications must play. Yet, with only a few exceptions, the functions of the modifications remain obscure. We investigate the bacterial enzymes responsible for generating 4-thiouridine and pseudouridine in tRNA.
Current techniques allow specific alteration of both the RNA and the enzymes, and with this ability to alter both enzyme and substrate precisely, the mode of recognition of RNA by the enzymes should be discernible. Finally, the discovery of catalytic RNA raises the intriguing possibility that the RNA molecule contributes functional groups that participate in the catalysis of modification.

We employ a wide array of techniques to study the different facets of these projects. We scrutinize genomic information for clues regarding the importance of particular amino acid residues and then use molecular biology to alter implicated amino acid residues and assess their functional impact. We synthesize both mechanism-based and competitive inhibitors as well as substrates and inhibitors with NMR-active nuclei so that we can harness this powerful technique to observe events at the active site. And we look for intermediates and obtain early kinetic time points using rapid chemical quench techniques. Graduates of the Mueller group, therefore, have a very broad range of skills and be well-versed in chemistry, biochemistry, and molecular biology. 
Click on the icon to find the sequence for any plasmid to which our papers refer.

For recent results, please go to Prof. Mueller's C.V. page and follow the links from the publication list.

Postdoctoral positions are currently available. Please follow this link for more information.